Biochemical characterization of archaeal homocitrate synthase from Sulfolobus acidocaldarius

FEBS Lett. 2020 Jan;594(1):126-134. doi: 10.1002/1873-3468.13550. Epub 2019 Aug 1.


The hyperthermophilic archaeon, Sulfolobus, synthesizes lysine via the α-aminoadipate pathway; however, the gene encoding homocitrate synthase, the enzyme responsible for the first and committed step of the pathway, has not yet been identified. In the present study, we identified saci_1304 as the gene encoding a novel type of homocitrate synthase fused with a Regulation of Amino acid Metabolism (RAM) domain at the C terminus in Sulfolobus acidocaldarius. Enzymatic characterization revealed that Sulfolobus homocitrate synthase was inhibited by lysine; however, the mutant enzyme lacking the RAM domain was insensitive to inhibition by lysine. The present results indicated that the RAM domain is responsible for enzyme inhibition.

Keywords: Archaea; RAM domain; homocitrate synthase; lysine biosynthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Archaeal Proteins / chemistry
  • Archaeal Proteins / genetics
  • Archaeal Proteins / metabolism*
  • Binding Sites
  • Lysine / metabolism
  • Mutation
  • Oxo-Acid-Lyases / chemistry
  • Oxo-Acid-Lyases / genetics
  • Oxo-Acid-Lyases / metabolism*
  • Protein Binding
  • Sulfolobus acidocaldarius / enzymology*


  • Archaeal Proteins
  • homocitrate synthase
  • Oxo-Acid-Lyases
  • Lysine